The majority of patients having formed a kidney stone composed of calcium oxalate alone or with apatite, when compared to normal subjects without a personal or family history of urinary stones, demonstrate hypercalciuria, impaired absolute renal Ca conservation, augmented fractional intestinal Ca absorption, accelerated skeletal Ca turnover and Ca crystalluria. In addition, they demonstrate hypophosphatemia and augmented fractional renal excretion of phosphate, a family history of kidney stones suggesting an autosomal dominant trait with inhibited expression in females, and, in preliminary studies, reduced serum 25-OH-vitamin D levels. The hypercalciuria among stone-formers has been attributed to a renal Ca leak with consequent secondary hyperparathyroidism. Alternatively, a primary defect in the regulation of phosphate metabolism may be responsible for augmented intestinal Ca absorption, skeletal Ca turnover and hypercalciuria since PO4 depletion in normal and thyroparathyroidectomized humans and dogs leads to maintenance of normal serum Ca and hypercalciuria. Moreover, PO4 depletion leads to accelerated production of 1,25-(OH)2-D3, the most potent form of the vitamin. We propose to evaluate in normal volunteers, the effects of dietary PO4-deprivation, (without Al(OH)3) on serum 25-OH-D, 1,25-(OH)2-D3 and PTH levels, the metabolism of 26,27-H3-25-OH-D3 or H3-C14-D3, Ca, P, Mg, Na, K, Cl, and acid balances, and renal clearances of ultrafilterable Ca and Mg. We also propose among calcium stone-formers and their hypercalciuric relatives to evaluate the renal response to dietary PO4 deprivation and, in separate studies assess serum 25-OH-D, 1,25-(OH)2-D3 and PTH levels, as well as the metabolism of 26-27-H3-25-OH-D3 and H3-C14-D3 before and after ongoing phosphate or hydrochlorothiazide therapy. BIBLIOGRAPHIC REFERENCES: Lemann, J., Jr., J.H. Dominguez and R.W. Gray. Idiopathic Hypercalciuria: A Defect in Phosphate and Vitamin D Metabolism? Proceedings of the International Colloquim on Renal Lithiasis, University of Florida, Gainesville, January, 1975 (in press).